title: A resurrection of 7-MEOTA: a comparison with tacrine.
abstract: Alzheimer´s disease (AD) is a progressive neurodegenerative dementia which currently represents one of the biggest threats for the human kind. The cure is still unknown and various hypotheses (cholinergic, amyloidal, oxidative, vascular etc.) are investigated in order to understand the pathophysiology of the disease and on this basis find an effective treatment. Tacrine, the first approved drug for the AD disease treatment, has been reported to be a multitargeted drug, however it was withdrawn from the market particularly due to its hepatotoxicity. Its derivative 7-methoxytacrine (7- MEOTA) probably due to the different metabolization does not exert this side effect. The aim of our study was to compare these two cholinesterase inhibitors from various, mainly cholinergic, points of view relevant for a potential AD drug. We found that 7-MEOTA does not fall behind its more well-known parent compound - tacrine. Furthermore, we found, that 7-MEOTA exerts better properties in most of the tests related to a possible AD treatment. Only the pharmacokinetics and a higher acetylcholinesterase and butyrylcholinesterase inhibitory potency would slightly give advantages to tacrine over 7-MEOTA, but concerning its lower toxicity, better antioxidant properties, interaction with muscarinic and nicotinic receptors and "safer" metabolization provide strong evidence for reconsider 7-MEOTA and its derivatives as candidate molecules for the treatment of AD.
authors.affiliation: Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 50005; Hradec Kralove, Czech Republic. ondrej.soukup@fnhk.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Soukup
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Jana
authors.initials: J
authors.lastname: Zdarova-Karasova
authors.forename: Jiri
authors.initials: J
authors.lastname: Patocka
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Jan
authors.initials: J
authors.lastname: Korabecny
authors.forename: Jan
authors.initials: J
authors.lastname: Krusek
authors.forename: Martina
authors.initials: M
authors.lastname: Kaniakova
authors.forename: Vendula
authors.initials: V
authors.lastname: Sepsova
authors.forename: Jana
authors.initials: J
authors.lastname: Mandikova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Trejtnar
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pohanka
authors.forename: Lucie
authors.initials: L
authors.lastname: Drtinova
authors.forename: Michal
authors.initials: M
authors.lastname: Pavlik
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tobin
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D013619:Tacrine; C016222:7-methoxytacrine